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Phenotype Ontology
Like Gene Ontology (GO), phenotypy ontology classifies and organizes gene-mutant/null phenotypic information from the very general at the top to more specific terms in the directed acyclic graph (DAG) by viewing an individual term as a node and its relations to parental terms (allowing for multiple parents) as directed edges. To navigate this hierarchy, we display all parental phenotypic terms to the current phenotypic term of interest ordered by their shortest distances to the current term. Also, only direct children phenotypic terms of the current phenotypic term are listed. Phenotype ontologies we have incorporated are as follows:

• Disease Ontology (DO) Ontology (DO)
  DO semantically integrates disease and medical vocabularies through extensive cross mapping of DO terms to MeSH, ICD, NCI thesaurus, SNOMED and OMIM.
  
• Human Phenotype (HP) Ontology (HP)
  HP captures phenotypic abnormalities that are described in OMIM, along with the corresponding disease-causing genes. It includes three complementary biological concepts: Mode_of_Inheritance (MI), ONset_and_clinical_course (ON), and Phenotypic_Abnormality (PA).
  
• Mouse Phenotype (MP) Ontology (MP)
  MP describes phenotypes of the mouse after a specific gene is genetically disrupted. Using it, Mouse Genome Informatics (MGI) provides high-coverate gene-level phenotypes for the mouse.
  
• Worm Phenotype (WP) Ontology (WP)
  WP classifies and organizes phenotype descriptions for C. elegans and other nematodes. Using it, WormBase provides primary resource for phenotype annotations for C. elegans.
  
• Yeast Phenotype (YP) Ontology (YP)
  Based on YP which is the major contributor to the Ascomycete phenotype ontology, Saccharomyces Genome Database (SGD) provides single mutant phenotypes for every gene in the yeast genome.
  
• Fly Phenotype (FP) Ontology (FP)
  FP refers to FlyBase controlled vocabulary. Specifically, a structured controlled vocabulary is used for the annotation of alleles (for their mutagen etc) in FlyBase.
  
• Fly Anatomy (FA) Ontology (FA)
  FA is a structured controlled vocabulary of the anatomy of Drosophila melanogaster, used for the description of phenotypes and where a gene is expressed.
  
• Zebrafish Anatomy (ZA) Ontology (ZA)
  ZA displays anatomical terms of the zebrafish using standard anatomical nomenclature, together with affected genes.
  
• Xenopus Anatomy (XA) Ontology (XA)
  XA represents the lineage of tissues and the timing of development for frogs (Xenopus laevis and Xenopus tropicalis). It is used to annotate Xenopus gene expression patterns and mutant and morphant phenotypes.
  
• Arabidopsis Plant Ontology (AP) Ontology (AP)
  As a major contributor to Plant Ontology which describes plant anatomical and morphological structures (AN) and growth and developmental stages (DE), the Arabidopsis Information Resource (TAIR) provides arabidopsis plant ontology annotations for the model higher plant Arabidopsis thaliana.
  
• Enzyme Commission (EC) Ontology (EC)
  Each enzyme is allocated a four-digit EC number, the first three digits of which define the reaction catalysed and the fourth of which is a unique identifier (serial number). Each enzyme is also assigned a systematic name that uniquely defines the reaction catalysed.
  
• DrugBank ATC (DB) Ontology (DB)
  In the Anatomical Therapeutic Chemical (ATC) classification system, drugs are classified in groups at five different levels according to the organ or system (1st level, anatomical main group) on which they act and their therapeutic (2nd level, therapeutic subgroup), pharmacological (3rd level, pharmacological subgroup) and chemical properties (4th level, chemical subgroup; 5th level, chemical substance). Only drugs in DrugBank are considered.
  
• UniProtKB KeyWords (KW) Ontology (KW)
  Keywords in UniProtKB are controlled vocabulary, providing a summary of the entry content and are used to index UniProtKB/Swiss-Prot entries based on 10 categories (the category "Technical term" being excluded here). Each keyword is attributed manually to UniProtKB/Swiss-Prot entries and automatically to UniProtKB/TrEMBL entries (according to specific annotation rules).
  
• UniProtKB UniPathway (UP) Ontology (UP)
  UP is a fully manually curated resource for the representation and annotation of metabolic pathways, being used as controlled vocabulary for pathway annotation in UniProtKB.
  

Structural Domain Phenotype Ontology and its Annotations
Structural Classification of Proteins (SCOP) classifies evolutionary-related domains into Superfamily level and Family level. Using the phenotype ontologies above, we have generated the domain-centric phenotype annotations, and further identified those phenotype terms which are the most informative to annotate SCOP domains. Promisingly, domain-centric phenotypic annotations can serve as an alternative starting point to explore genotype-phenotype relationships. We provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Structural Domain Disease Ontology (DO) Ontology (SDDO) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DO.txt, and the corresponding ontology:SDDO.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Human Phenotype (HP) Ontology (SDHP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2HP.txt, and the corresponding ontology:SDHP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Mouse Phenotype (MP) Ontology (SDMP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2MP.txt, and the corresponding ontology:SDMP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Worm Phenotype (WP) Ontology (SDWP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2WP.txt, and the corresponding ontology:SDWP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Yeast Phenotype (YP) Ontology (SDYP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2YP.txt, and the corresponding ontology:SDYP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Phenotype (FP) Ontology (SDFP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FP.txt, and the corresponding ontology:SDFP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Anatomy (FA) Ontology (SDFA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FA.txt, and the corresponding ontology:SDFA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Zebrafish Anatomy (ZA) Ontology (SDZA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2ZA.txt, and the corresponding ontology:SDZA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Xenopus Anatomy (XA) Ontology (SDXA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2XA.txt, and the corresponding ontology:SDXA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Arabidopsis Plant Ontology (AP) Ontology (SDAP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2AP.txt, and the corresponding ontology:SDAP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Enzyme Commission (EC) Ontology (SDEC) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2EC.txt, and the corresponding ontology:SDEC.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain DrugBank ATC (DB) Ontology (SDDB) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DB.txt, and the corresponding ontology:SDDB.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB KeyWords (KW) Ontology (SDKW) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2KW.txt, and the corresponding ontology:SDKW.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB UniPathway (UP) Ontology (SDUP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2UP.txt, and the corresponding ontology:SDUP.txt) and mysql tables (Domain2PO.sql.gz).
  

Supra-domain Phenotype Ontology and its Annotations
Although domain-centric annotations hold great promise in describing phenotypic nature of independent domains, most domains themselves may not just work alone. In multi-domain proteins, they may be combined together to form distinct domain architectures. The recombination of the existing domains is considered as one of major driving forces for phenotypic diversificaation. As an extension, we have also generated supra-domain phenotype ontology and its annotations. Compared to domain-centric phenotype ontology and annotations (SCOP domains at the Superfamily level and Family level), this version focuses on supra-domains and individual SCOP domains ONLY at the Superfamily level. Besides, in terms of individual superfamilies, their annotations from the domain-centric version may be different from those from supra-domains version. Depending on your focus, the former should be used for the consideration of both the Superfamily level and Family level, otherwise the latter should be used if you are interested in domain combinations. Also, we provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Supra-domain Domain Disease Ontology (DO) Ontology (SPDO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DO.txt, and the corresponding ontology:SPDO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Human Phenotype (HP) Ontology (SPHO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2HP.txt, and the corresponding ontology:SPHO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Mouse Phenotype (MP) Ontology (SPMP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2MP.txt, and the corresponding ontology:SPMP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Worm Phenotype (WP) Ontology (SPWP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2WP.txt, and the corresponding ontology:SPWP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Yeast Phenotype (YP) Ontology (SPYP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2YP.txt, and the corresponding ontology:SPYP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Phenotype (FP) Ontology (SPFP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FP.txt, and the corresponding ontology:SPFP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Anatomy (FA) Ontology (SPFA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FA.txt, and the corresponding ontology:SPFA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Zebrafish Anatomy (ZA) Ontology (SPZA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2ZA.txt, and the corresponding ontology:SPZA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Xenopus Anatomy (XA) Ontology (SPXA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2XA.txt, and the corresponding ontology:SPXA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Arabidopsis Plant Ontology (AP) Ontology (SPAP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2AP.txt, and the corresponding ontology:SPAP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Enzyme Commission (EC) Ontology (SPEC) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2EC.txt, and the corresponding ontology:SPEC.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain DrugBank ATC (DB) Ontology (SPDB) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DB.txt, and the corresponding ontology:SPDB.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB KeyWords (KW) Ontology (SPKW) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2KW.txt, and the corresponding ontology:SPKW.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB UniPathway (UP) Ontology (SPUP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2UP.txt, and the corresponding ontology:SPUP.txt) and mysql tables (SP2PO.sql.gz).
  

Superfamily domains annotated to this FA term (SDFA level: Least Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain	0	DIRECT
cAMP-binding domain-like	0	DIRECT
PX domain	0	DIRECT
SAP domain	0	DIRECT
Rhomboid-like	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
Putative DNA-binding domain	0	DIRECT
alpha-catenin/vinculin-like	0	DIRECT
Rhodanese/Cell cycle control phosphatase	0	DIRECT
Orange domain-like	0	DIRECT
Plexin repeat	0	DIRECT
Sema domain	0	DIRECT
TIMP-like	0	DIRECT
Regulator of G-protein signaling, RGS	0	DIRECT
L27 domain	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
PreATP-grasp domain	0	DIRECT
Cullin homology domain	0	DIRECT
lambda repressor-like DNA-binding domains	0	DIRECT
Second domain of FERM	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
MIR domain	0	DIRECT
Serpins	0	DIRECT
Periplasmic binding protein-like I	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
RCC1/BLIP-II	0	DIRECT
L30e-like	0	DIRECT
Smc hinge domain	0	DIRECT
Multidrug resistance efflux transporter EmrE	0	DIRECT
Integrin domains	0	DIRECT
Mob1/phocein	0	DIRECT
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
Clathrin adaptor appendage domain	0	DIRECT
Kazal-type serine protease inhibitors	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
SAICAR synthase-like	0	DIRECT
ARID-like	0	DIRECT
Cytokine	0	DIRECT
Cullin repeat-like	0	DIRECT
Thiamin diphosphate-binding fold (THDP-binding)	0	DIRECT
SMAD MH1 domain	0	DIRECT
Homeodomain-like	0.0000000001533	DIRECT
beta-beta-alpha zinc fingers	0.000005513	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.000006275	DIRECT
Fibronectin type III	0.000473	DIRECT
Immunoglobulin	0.002779	INHERITED FROM: connective || LN period neuron || leg taste bristle chemosensory neuron || neuropil glial sheath || nerve || abdominal segmental nerve || embryonic/larval peripheral nervous system || abdominal nerve || synaptic neuropil || tract neuropil || commissure || LNv neuron
Protein kinase-like (PK-like)	0.003243	INHERITED FROM: intestinal stem cell || synaptic neuropil
Nuclear receptor ligand-binding domain	0.01077	INHERITED FROM: protocerebrum || central brain || synaptic neuropil block || supraesophageal ganglion neuron || neuropil || mushroom body gamma-lobe || synaptic neuropil
p53-like transcription factors	0.01077	INHERITED FROM: adult external thorax || tagmatic subdivision of integument || mesothoracic tergum
Glucocorticoid receptor-like (DNA-binding domain)	0.01106	INHERITED FROM: region of integument || adult external thorax
SH2 domain	0.01122	INHERITED FROM: midline crossing tract || wing blade || ommatidium || adult peripheral nervous system || photoreceptor cell R7
PH domain-like	0.0185	INHERITED FROM: embryonic foregut
HMG-box	0.04358	INHERITED FROM: adult external thorax || wing
Cystine-knot cytokines	0.07145	INHERITED FROM: embryonic/larval spiracle || stigmatophore || embryonic/larval posterior spiracle
EGF/Laminin	0.1065	INHERITED FROM: wing blade || eye photoreceptor cell stalk || embryonic/larval midgut cell || adult midgut progenitor cell || larval caeca region || proventriculus || tendon cell || ventral nervous system || ocellus
Transducin (alpha subunit), insertion domain	0.2001	INHERITED FROM: eo neuron
Snake toxin-like	0.2001	INHERITED FROM: tarsal segment || embryonic/larval neuromuscular junction || wing cell || wing vein
Toll/Interleukin receptor TIR domain	0.2001	INHERITED FROM: ventral nerve cord
Growth factor receptor domain	0.2627	INHERITED FROM: embryonic/larval midline of ventral nerve cord || wing vein L2 || surface associated glial cell || vMP2 neuron || dMP2 neuron || proventriculus || embryonic fiber tract || ventral nervous system || integumentary specialisation || ocellar triangle || hindgut || photoreceptor cell R7 || ocellus || RP2sib neuron
Spectrin repeat	0.2793	INHERITED FROM: longitudinal connective || connective || ipsilateral tract || copper cell || midgut enterocyte || tract || middle midgut
vWA-like	0.3427	INHERITED FROM: endocuticular specialization
(Phosphotyrosine protein) phosphatases II	0.3546	INHERITED FROM: medial lobe of adult mushroom body || intersegmental nerve
Cytochrome P450	0.3878	INHERITED FROM: midline crossing tract || embryonic/larval foregut || embryonic/larval hindgut || midline glial cell || CNS glial cell || neuropil glial sheath || larval VNC neuropil glial cell || neuropil associated CNS glial cell || tract || midgut || larval neuropil glial cell || tract neuropil || hindgut || commissure
HAD-like	0.4185	INHERITED FROM: rhabdomere of eye photoreceptor cell
SET domain	0.457	INHERITED FROM: metathoracic leg || haltere
BAR/IMD domain-like	0.4824	INHERITED FROM: neuromuscular junction || NMJ bouton
dsRNA-binding domain-like	0.4824	INHERITED FROM: projection neuron || adult MBp lineage clone || mushroom body extrinsic neuron || alpha/beta Kenyon cell || medial antennal lobe tract projection neuron || antennal lobe projection neuron || Kenyon cell || adult antennal lobe projection neuron || adult uniglomerular antennal lobe projection neuron adPN || uniglomerular antennal lobe projection neuron || adult antennal lobe projection neuron DL1 adPN || antennal lobe projection neuron adPN || adult MBp lineage neuron || adult antennal lobe projection neuron adPN || unilateral ACT relay interneuron || persistent antennal lobe projection neuron
Cadherin-like	0.5376	INHERITED FROM: photoreceptor cell R4
TPR-like	0.9679	INHERITED FROM: antennal nerve || adult antennal nerve

Family domains annotated to this FA term (SDFA level: Least Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
Eps15 homology domain (EH domain)	0	DIRECT
ARID domain	0	DIRECT
Extracellular domain of cell surface receptors	0	DIRECT
Forkhead DNA-binding domain	0	DIRECT
Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain	0	DIRECT
Rel/Dorsal transcription factors, DNA-binding domain	0	DIRECT
cAMP-binding domain	0	DIRECT
Phoshoinositide 3-kinase (PI3K), catalytic domain	0	DIRECT
Regulator of G-protein signaling, RGS	0	DIRECT
Smc hinge domain	0	DIRECT
Serpins	0	DIRECT
Diacylglycerol kinase-like	0	DIRECT
Dachshund-homology domain	0	DIRECT
Myb/SANT domain	0	DIRECT
EF-hand modules in multidomain proteins	0	DIRECT
Pepsin-like	0	DIRECT
SPRY domain	0	DIRECT
BC ATP-binding domain-like	0	DIRECT
Rhomboid-like	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
Phoshoinositide 3-kinase (PI3K) helical domain	0	DIRECT
Laminin-type module	0	DIRECT
Transforming growth factor (TGF)-beta	0	DIRECT
Plexin repeat	0	DIRECT
Third domain of FERM	0	DIRECT
L27 domain	0	DIRECT
Arrestin/Vps26-like	0	DIRECT
Cell cycle control phosphatase, catalytic domain	0	DIRECT
SAP domain	0	DIRECT
Mob1/phocein	0	DIRECT
Class I glutamine amidotransferases (GAT)	0	DIRECT
Hairy Orange domain	0	DIRECT
RNase III catalytic domain-like	0	DIRECT
SMAD MH1 domain	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
BC N-terminal domain-like	0	DIRECT
Synaptotagmin-like (S variant)	0	DIRECT
Fibroblast growth factors (FGF)	0	DIRECT
Erythroid transcription factor GATA-1	0	DIRECT
First domain of FERM	0	DIRECT
Ubiquitin carboxyl-terminal hydrolase UCH-L	0	DIRECT
Sema domain	0	DIRECT
p120GAP domain-like	0	DIRECT
POU-specific domain	0	DIRECT
L-arabinose binding protein-like	0	DIRECT
Phosphatidylinositol phosphate kinase IIbeta, PIPK IIbeta	0	DIRECT
SCF ubiquitin ligase complex WHB domain	0	DIRECT
Cullin homology domain	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
Integrin domains	0	DIRECT
Cullin repeat	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
PX domain	0	DIRECT
NF-kappa-B/REL/DORSAL transcription factors, C-terminal domain	0	DIRECT
Single strand DNA-binding domain, SSB	0	DIRECT
Phosphate binding protein-like	0	DIRECT
Ubiquitin carboxyl-terminal hydrolase, UCH	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
Second domain of FERM	0	DIRECT
MIR domain	0	DIRECT
Choline/Carnitine O-acyltransferase	0	DIRECT
Homeodomain	0.000000000004015	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.00001073	DIRECT
Fibronectin type III	0.0006876	DIRECT
Protein kinases, catalytic subunit	0.003053	INHERITED FROM: intestinal stem cell || synaptic neuropil || photoreceptor cell R8 of pale ommatidium
Classic zinc finger, C2H2	0.00547	INHERITED FROM: region of integument
Nuclear receptor ligand-binding domain	0.01107	INHERITED FROM: protocerebrum || central brain || synaptic neuropil block || supraesophageal ganglion neuron || neuropil || mushroom body gamma-lobe || synaptic neuropil
SH2 domain	0.01239	INHERITED FROM: midline crossing tract || wing blade || ommatidium || adult peripheral nervous system || photoreceptor cell R7
Nuclear receptor	0.02682	INHERITED FROM: abdominal neuromere || synaptic neuropil block || larval abdominal neuromere || supraesophageal ganglion neuron || mushroom body gamma-lobe
HMG-box	0.04438	INHERITED FROM: adult external thorax || wing
Higher-molecular-weight phosphotyrosine protein phosphatases	0.06292	INHERITED FROM: intersegmental nerve
Paired domain	0.06292	INHERITED FROM: EG neuron || RP2 motor neuron || EL neuron
Ngr ectodomain-like	0.06292	INHERITED FROM: intersegmental nerve of A1-7 || abdominal intersegmental nerve || intersegmental nerve branch ISNb of A1-7
I set domains	0.0863	INHERITED FROM: connective || LN period neuron || leg taste bristle chemosensory neuron || neuropil glial sheath || synaptic neuropil block || segmental subdivision of organ system || s-LNv neuron || synaptic neuropil || antennal lobe glomerulus || gustatory receptor neuron || interface glial cell || tract neuropil || commissure || adult brain || LNv neuron
Histone lysine methyltransferases	0.11	INHERITED FROM: metathoracic leg || haltere
PLC-like (P variant)	0.11	INHERITED FROM: larval dorsal multidendritic neuron ddaC || larval dorsal multidendritic neuron || mesothoracic tergum
Transducin (alpha subunit), insertion domain	0.1918	INHERITED FROM: eo neuron
Toll/Interleukin receptor TIR domain	0.1918	INHERITED FROM: ventral nerve cord
Calponin-homology domain, CH-domain	0.2305	INHERITED FROM: abdominal segmental nerve
SMAD domain	0.2517	INHERITED FROM: wing blade || gut section || wing vein
Spectrin repeat	0.2763	INHERITED FROM: longitudinal connective || connective || ipsilateral tract || copper cell || midgut enterocyte || tract || middle midgut
Ankyrin repeat	0.291	INHERITED FROM: ventral multidendritic neuron
SAM (sterile alpha motif) domain	0.3392	INHERITED FROM: mesothoracic leg || prothoracic leg || prothoracic tarsal segment || metatarsus of male prothoracic leg || prothoracic metatarsus || metatarsus || sex comb
Cytochrome P450	0.3915	INHERITED FROM: midline crossing tract || embryonic/larval foregut || embryonic/larval hindgut || midline glial cell || CNS glial cell || neuropil glial sheath || larval VNC neuropil glial cell || neuropil associated CNS glial cell || tract || midgut || larval neuropil glial cell || tract neuropil || hindgut || commissure
Cyclin	0.4238	INHERITED FROM: tagmatic subdivision of organ system
Growth factor receptor domain	0.4621	INHERITED FROM: dorsocentral bristle || salivary gland || proventriculus || tibia || integumentary specialisation || ocellar triangle || hindgut || ocellus
EGF-type module	0.5941	INHERITED FROM: wing blade || adult external head || embryonic/larval midgut cell || adult midgut progenitor cell || proventriculus || ventral nervous system || hindgut
Ubiquitin-related	0.5969	INHERITED FROM: mushroom body extrinsic neuron
Cadherin	0.6253	INHERITED FROM: outer photoreceptor cell || photoreceptor cell R4
G proteins	0.7714	INHERITED FROM: wing hair

Trees by TreeVector

A presence/absence matrix is generated using protein domain architecture data for all genomes in SUPERFAMILY. The PAUP software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Single)	FDR (all)	Annotation (direct or inherited)
cAMP-binding domain-like	0	DIRECT
Cytokine	0	DIRECT
TIMP-like	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
Sema domain	0	DIRECT
Cullin homology domain	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
PreATP-grasp domain	0	DIRECT
Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain	0	DIRECT
MIR domain	0	DIRECT
RCC1/BLIP-II	0	DIRECT
Smc hinge domain	0	DIRECT
ARID-like	0	DIRECT
Second domain of FERM	0	DIRECT
Rhodanese/Cell cycle control phosphatase	0	DIRECT
Integrin domains	0	DIRECT
L27 domain	0	DIRECT
Regulator of G-protein signaling, RGS	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
Plexin repeat	0	DIRECT
SMAD MH1 domain	0	DIRECT
Putative DNA-binding domain	0	DIRECT
lambda repressor-like DNA-binding domains	0	DIRECT
Rhomboid-like	0	DIRECT
Clathrin adaptor appendage domain	0	DIRECT
Cullin repeat-like	0	DIRECT
SAICAR synthase-like	0	DIRECT
Kazal-type serine protease inhibitors	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
Periplasmic binding protein-like I	0	DIRECT
L30e-like	0	DIRECT
Serpins	0	DIRECT
SAP domain	0	DIRECT
alpha-catenin/vinculin-like	0	DIRECT
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
Multidrug resistance efflux transporter EmrE	0	DIRECT
Mob1/phocein	0	DIRECT
Thiamin diphosphate-binding fold (THDP-binding)	0	DIRECT
Orange domain-like	0	DIRECT
PX domain	0	DIRECT
Homeodomain-like	0.0000000001096	DIRECT
beta-beta-alpha zinc fingers	0.00000401	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.000004563	DIRECT
Fibronectin type III	0.0003472	DIRECT
Immunoglobulin	0.002013	INHERITED FROM: synaptic neuropil || connective || leg taste bristle chemosensory neuron || antennal lobe glomerulus || central nervous system || nerve || commissure || abdominal segmental nerve || LN period neuron || LNv neuron || embryonic/larval peripheral nervous system || neuropil glial sheath || tract neuropil || abdominal nerve
Protein kinase-like (PK-like)	0.002351	INHERITED FROM: synaptic neuropil || photoreceptor cell R8 of pale ommatidium || intestinal stem cell
p53-like transcription factors	0.008062	INHERITED FROM: tagmatic subdivision of integument || adult external thorax || tract || integumentary process || mesothoracic tergum
Nuclear receptor ligand-binding domain	0.008062	INHERITED FROM: central brain || synaptic neuropil || synaptic neuropil block || mushroom body gamma-lobe || protocerebrum || neuropil || supraesophageal ganglion neuron
Glucocorticoid receptor-like (DNA-binding domain)	0.008288	INHERITED FROM: region of integument || adult external thorax
SH2 domain	0.008406	INHERITED FROM: photoreceptor cell R7 || ommatidium || connective || wing blade || midline crossing tract || adult peripheral nervous system
PH domain-like	0.01419	INHERITED FROM: embryonic foregut
HMG-box	0.03437	INHERITED FROM: adult external thorax || wing
Cystine-knot cytokines	0.05822	INHERITED FROM: embryonic/larval posterior spiracle || stigmatophore || spiracle || embryonic/larval spiracle
EGF/Laminin	0.08904	INHERITED FROM: eye photoreceptor cell stalk || ocellus || adult midgut progenitor cell || larval caeca region || wing blade || ventral nervous system || embryonic/larval midgut cell || tendon cell || proventriculus
GTPase activation domain, GAP	0.1317	INHERITED FROM: abdominal intersegmental nerve
Transducin (alpha subunit), insertion domain	0.1749	INHERITED FROM: eo neuron
Snake toxin-like	0.1749	INHERITED FROM: wing vein || wing cell || embryonic/larval neuromuscular junction || tarsal segment || adult optic lobe
Toll/Interleukin receptor TIR domain	0.1749	INHERITED FROM: ventral nerve cord
Calponin-homology domain, CH-domain	0.199	INHERITED FROM: abdominal segmental nerve
Growth factor receptor domain	0.2333	INHERITED FROM: photoreceptor cell R7 || ocellus || hindgut || wing vein L4 || wing vein L2 || RP2sib neuron || vMP2 neuron || retinal pigment cell || integumentary specialisation || embryonic/larval midline of ventral nerve cord || dMP2 neuron || surface associated glial cell || fascicle || ocellar triangle || ventral nervous system || embryonic fiber tract || proventriculus
Spectrin repeat	0.2495	INHERITED FROM: ipsilateral tract || connective || tract || longitudinal connective || middle midgut || midgut enterocyte || copper cell
vWA-like	0.3108	INHERITED FROM: endocuticular specialization
(Phosphotyrosine protein) phosphatases II	0.3226	INHERITED FROM: medial lobe of adult mushroom body || intersegmental nerve
Cytochrome P450	0.3553	INHERITED FROM: embryonic/larval hindgut || hindgut || larval neuropil glial cell || embryonic/larval foregut || larval VNC neuropil glial cell || commissure || tract || CNS glial cell || midgut || midline crossing tract || neuropil associated CNS glial cell || midline glial cell || neuropil glial sheath || tract neuropil
HAD-like	0.3855	INHERITED FROM: rhabdomere of eye photoreceptor cell
SET domain	0.4246	INHERITED FROM: metathoracic leg || haltere
BAR/IMD domain-like	0.4501	INHERITED FROM: neuromuscular junction || NMJ bouton
dsRNA-binding domain-like	0.4501	INHERITED FROM: adult MBp lineage neuron || Kenyon cell || alpha/beta Kenyon cell || medial antennal lobe tract projection neuron || antennal lobe projection neuron || adult antennal lobe projection neuron || antennal lobe projection neuron adPN || uniglomerular antennal lobe projection neuron || adult uniglomerular antennal lobe projection neuron adPN || persistent antennal lobe projection neuron || unilateral ACT relay interneuron || mushroom body extrinsic neuron || projection neuron || adult antennal lobe projection neuron DL1 adPN || adult antennal lobe projection neuron adPN || adult MBp lineage clone
Cadherin-like	0.5061	INHERITED FROM: photoreceptor cell R4
TPR-like	0.9617	INHERITED FROM: antennal nerve || adult antennal nerve

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Duplex) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
74788,75632 74788 - Cullin repeat-like 75632 - Cullin homology domain	0	DIRECT
47031,50729 47031 - Second domain of FERM 50729 - PH domain-like	0	DIRECT
52058,48726 52058 - L domain-like 48726 - Immunoglobulin	0	DIRECT
57903,47370 57903 - FYVE/PHD zinc finger 47370 - Bromodomain	0	DIRECT
47413,46689 47413 - lambda repressor-like DNA-binding domains 46689 - Homeodomain-like	0	DIRECT
49562,49562 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 49562 - C2 domain (Calcium/lipid-binding domain, CaLB)	0	DIRECT
52440,56059 52440 - PreATP-grasp domain 56059 - Glutathione synthetase ATP-binding domain-like	0	DIRECT
55550,56112 55550 - SH2 domain 56112 - Protein kinase-like (PK-like)	0	DIRECT
101912,103575 101912 - Sema domain 103575 - Plexin repeat	0	DIRECT
57716,48508 57716 - Glucocorticoid receptor-like (DNA-binding domain) 48508 - Nuclear receptor ligand-binding domain	0	DIRECT
51045,51045 51045 - WW domain 51045 - WW domain	0	DIRECT
48425,50729 48425 - Sec7 domain 50729 - PH domain-like	0	DIRECT
49562,48371 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 48371 - ARM repeat	0	DIRECT
47769,47769 47769 - SAM/Pointed domain 47769 - SAM/Pointed domain	0	DIRECT
49417,81296 49417 - p53-like transcription factors 81296 - E set domains	0	DIRECT
57903,57903 57903 - FYVE/PHD zinc finger 57903 - FYVE/PHD zinc finger	0	DIRECT
81660,56784 81660 - Metal cation-transporting ATPase, ATP-binding domain N 56784 - HAD-like	0	DIRECT
75632,46785 75632 - Cullin homology domain 46785 - "Winged helix" DNA-binding domain	0	DIRECT
81383,52047 81383 - F-box domain 52047 - RNI-like	0	DIRECT
52058,52058 52058 - L domain-like 52058 - L domain-like	0	DIRECT
51206,51206 51206 - cAMP-binding domain-like 51206 - cAMP-binding domain-like	0	DIRECT
47220,47220 47220 - alpha-catenin/vinculin-like 47220 - alpha-catenin/vinculin-like	0	DIRECT
48371,56112 48371 - ARM repeat 56112 - Protein kinase-like (PK-like)	0	DIRECT
55550,50044 55550 - SH2 domain 50044 - SH3-domain	0	DIRECT
52777,52777 52777 - CoA-dependent acyltransferases 52777 - CoA-dependent acyltransferases	0	DIRECT
47459,158457 47459 - HLH, helix-loop-helix DNA-binding domain 158457 - Orange domain-like	0	DIRECT
50044,55550 50044 - SH3-domain 55550 - SH2 domain	0	DIRECT
48403,48403 48403 - Ankyrin repeat 48403 - Ankyrin repeat	0	DIRECT
49265,49265 49265 - Fibronectin type III 49265 - Fibronectin type III	0	DIRECT
54236,47031 54236 - Ubiquitin-like 47031 - Second domain of FERM	0	DIRECT
57667,57667 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers	0.00001118	DIRECT
48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin	0.02415	INHERITED FROM: segmental subdivision of organ system || synaptic neuropil || synaptic neuropil block || connective || leg taste bristle chemosensory neuron || antennal lobe glomerulus || central nervous system || commissure || s-LNv neuron || LNv neuron || neuropil glial sheath || tract neuropil
48726,49265 48726 - Immunoglobulin 49265 - Fibronectin type III	0.05409	INHERITED FROM: adult antennal lobe glomerulus || connective || leg taste bristle chemosensory neuron || antennal lobe glomerulus || gustatory receptor neuron || commissure || s-LNv neuron || giant fiber neuron || LNv neuron || neuropil associated CNS glial cell || lobe system of adult mushroom body || adult antennal lobe || tract neuropil
49899,49899 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0.07214	INHERITED FROM: photoreceptor cell R4 || peripheral nervous system
46966,46966 46966 - Spectrin repeat 46966 - Spectrin repeat	0.09713	INHERITED FROM: ipsilateral tract || connective || tract || longitudinal connective || middle midgut || midgut enterocyte || copper cell || adult protocerebrum || tract neuropil
47895,52540 47895 - Transducin (alpha subunit), insertion domain 52540 - P-loop containing nucleoside triphosphate hydrolases	0.1749	INHERITED FROM: eo neuron
47459,55785 47459 - HLH, helix-loop-helix DNA-binding domain 55785 - PYP-like sensor domain (PAS domain)	0.1749	INHERITED FROM: sclerite
57196,57184 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.1749	INHERITED FROM: joint || wing vein || photoreceptor cell R7 || scutum || intersegmental nerve || leg || inner photoreceptor cell || integumentary specialisation || wing blade dorsal compartment || proventriculus
81296,81296 81296 - E set domains 81296 - E set domains	0.235	INHERITED FROM: intersegmental nerve || abdominal segmental nerve || abdominal intersegmental nerve || segmental nerve || abdominal nerve
50156,50044 50156 - PDZ domain-like 50044 - SH3-domain	0.3135	INHERITED FROM: embryonic/larval peripheral nervous system
52799,52799 52799 - (Phosphotyrosine protein) phosphatases II 52799 - (Phosphotyrosine protein) phosphatases II	0.3135	INHERITED FROM: intersegmental nerve || nerve || abdominal segmental nerve || embryonic/larval peripheral nervous system || segmental nerve || abdominal nerve
57196,57196 57196 - EGF/Laminin 57196 - EGF/Laminin	0.3521	INHERITED FROM: joint || secondary pigment cell || eye photoreceptor cell stalk || ocellus || postfrons || intersegmental nerve branch ISNb of A1-7 || ventral nervous system || frons || wing blade dorsal compartment || proventriculus || tertiary pigment cell
57184,57196 57184 - Growth factor receptor domain 57196 - EGF/Laminin	0.3877	INHERITED FROM: integumentary specialisation
49313,49313 49313 - Cadherin-like 49313 - Cadherin-like	0.5938	INHERITED FROM: photoreceptor cell R4 || outer photoreceptor cell || wing hair

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Triple) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
57196,49899,49899 57196 - EGF/Laminin 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0	DIRECT
74788,75632,46785 74788 - Cullin repeat-like 75632 - Cullin homology domain 46785 - "Winged helix" DNA-binding domain	0	DIRECT
52058,52058,52058 52058 - L domain-like 52058 - L domain-like 52058 - L domain-like	0	DIRECT
46966,46966,46966 46966 - Spectrin repeat 46966 - Spectrin repeat 46966 - Spectrin repeat	0	DIRECT
49562,48371,56112 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 48371 - ARM repeat 56112 - Protein kinase-like (PK-like)	0	DIRECT
54236,47031,50729 54236 - Ubiquitin-like 47031 - Second domain of FERM 50729 - PH domain-like	0	DIRECT
49899,49899,49899 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0	DIRECT
81660,56784,81665 81660 - Metal cation-transporting ATPase, ATP-binding domain N 56784 - HAD-like 81665 - Calcium ATPase, transmembrane domain M	0	DIRECT
81296,81296,81296 81296 - E set domains 81296 - E set domains 81296 - E set domains	0	DIRECT
57667,57667,57667 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers	0.00018	DIRECT
48726,48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin 48726 - Immunoglobulin	0.1048	INHERITED FROM: synaptic neuropil || connective || leg taste bristle chemosensory neuron || gustatory receptor neuron || commissure || s-LNv neuron || LNv neuron || tract neuropil
48726,48726,49265 48726 - Immunoglobulin 48726 - Immunoglobulin 49265 - Fibronectin type III	0.1063	INHERITED FROM: adult antennal lobe glomerulus || connective || leg taste bristle chemosensory neuron || antennal lobe glomerulus || gustatory receptor neuron || s-LNv neuron || giant fiber neuron || eo neuron || LNv neuron || neuropil associated CNS glial cell || lobe system of adult mushroom body || neuropil glial sheath || embryonic/larval central nervous system || adult antennal lobe
57196,57196,57196 57196 - EGF/Laminin 57196 - EGF/Laminin 57196 - EGF/Laminin	0.1229	INHERITED FROM: joint || photoreceptor cell R1 || secondary pigment cell || eye photoreceptor cell stalk || ocellus || postfrons || photoreceptor cell R6 || ocellar triangle || ventral nervous system || frons || wing blade dorsal compartment || adult external head || proventriculus || tertiary pigment cell
57196,57196,57184 57196 - EGF/Laminin 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.235	INHERITED FROM: dorsal mesothorax || adult external mesothorax || scutum || intersegmental nerve || nerve || adult thoracic mechanosensory chaeta || integumentary specialisation || tergum || mesothoracic tergum
49313,49313,49313 49313 - Cadherin-like 49313 - Cadherin-like 49313 - Cadherin-like	0.5938	INHERITED FROM: photoreceptor cell R4 || outer photoreceptor cell || wing hair

Trees by TreeVector

A presence/absence matrix is generated using protein domains and supradomains for all genomes in SUPERFAMILY. The RAxML software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.